Electrical activity in the human heart originates in the right atrium (RA) in the sinoatrial (SA) node as a wave. This wave of activation spreads quickly across the atria to the atrioventricular (AV) node. The AV node serves to delay the wave of activation relative to activation of the ventricle. The delay results in contraction of the atrium before the ventricles contract. After the activation is delayed by the AV node, the activation wave enters and excites the bundle of His. Excitation of the bundle of His results in propagation through the Purkinje fibers of a plane wave structure across the ventricles through the ventricular conduction system. Excitation spreading through the conduction system activates each ventricular cell at a precise time relative to activation from the bundle of His (known as the “Phase”) to produce a phased ventricular contraction. For regular cardiac contraction, both atrial and ventricular, it is important that each contractile cell possess only one phase value during a contraction cycle. When these phases multiply within a contractile cycle, the result is arrhythmia.
In the case of ventricular arrhythmias, for various reasons both conductive and structural, the function of the AV node can be compromised (AV block). AV block inhibits or prevents utilization of the normal conduction systems of the ventricles. Ventricular pacing has been used for treating heart rhythm disorders when a normal conduction system (free of heterogeneities) cannot be utilized due to AV block. However, ventricular pacing does not reproduce the precise wave front structure characteristic of the AV node, which is responsible for the optimal spatial and temporal electrical actuation of the ventricular cells that is required for optimal hemodynamic function of the heart. Pacing induced inefficiency has been associated with an increased occurrence of congestive heart failure, desynchronized contractions, negative inotropic effects, histological and ultra-structural changes in ventricular tissue.
Alternative pacing sites, for example, the right ventricle (RV) generally, RV outflow tract (RVOT) and various septum sites have been investigated relative to improving cardiac hemodynamics during pacing. Direct His bundle pacing has also been used in an attempt to achieve synchronized ventricular contraction in patients with an intact ventricular conduction system. However there can be limitations associated with His bundle pacing in humans. For example, studies have reported difficulty in pacing the relatively small area of the His bundle and difficulty inserting a pacing lead into the membranous septum. Further, higher pacing and lower sensing thresholds can be required for His pacing than for RV pacing due to the high fibrous content of the His region. Also, because His bundle pacing site is located close to the aorta, there are potentially devastating consequences due to damage of the aorta.
Single source pacing modalities universally are incapable of reproducing the synchrony achieved by a healthy AV node. Accordingly, resynchronization therapy has been advanced by utilizing multiple ventricular pacing sites, such as biventricular pacing. While the multiple-lead approach provides greater versatility in achieving the required physiological degree of synchrony, control algorithms have not been devised to take advantage of this increased control dimensionality.
One form of regularization is cardioversion. Cardioversion attempts to reset all electric activity in the atria and requires the use of large (5V/cm) electric field gradients. These high energies cause pain and trauma for the patient, damage the myocardium, and reduce battery life in implanted devices. Another strategy, anti-tachycardia pacing (ATP), seeks to avoid the development of permanent atrial fibrillation (AF) by suppressing paroxysmal AF. ATP consists of a train of 8 to 10 low-energy stimuli delivered as a pacing ramp or burst at 50 Hz via a single pacing electrode. ATP is effective in treating spontaneous atrial tachyarrhythmia, especially slower tachycardia, but it is not very effective for converting AF.
Predicting propagation patterns of the in situ heart is an arduous task, especially when the anatomic and functional complexity of a diseased heart is considered. Technical challenges are involved in recording propagation patterns in an intact organ at temporal and spatial resolution sufficient to reveal the interactions of rotating waves and paced wave fronts.
The pacing aspect is especially complicated. After an electric field pulse is applied to the heart, “virtual electrodes” may arise at interfaces separating regions with different conductivities. These sites may be macroscopic, such as blood vessels or ischemic regions, or smaller-scale discontinuities, including areas of fibrosis or abrupt changes in fiber direction. Virtual electrodes arise when the activation wave energy is re-radiated in a manner analogous to optical reflection and diffraction from tissue conductive and structure discontinuities. In the application of pacing pulses, a virtual electrode is a secondary source of an activation wave. The character of this secondary activation wave is highly dependent on the extent of the conductivity discontinuity and the strength of the applied electric field.
Consider now how an activation site develops on application of an electric field in cardiac tissue containing a generic conductivity discontinuity between myocardium and an inexcitable inhomogeneity. When an electric field is applied, current flows out of the electrode and through the extracellular medium and enters the tissue at the tissue edge and subsequently exits at the boundary of the inexcitable region. Similarly, on the other side of the inexcitable region, current re-enters the tissue at the boundary. In quiescent tissue, this current produces depolarization (hyperpolarization), and in the conducting region along all interface boundaries where the excitable tissue is closer to the electrode. If the depolarized region reaches the threshold for excitation, it can initiate propagating waves, thereby serving as an activation site, also known as a secondary source, or virtual electrode.
Virtual electrode formation has been demonstrated to terminate fast atrial tachycardias and AF. In this method, electrodes located at a small distance from the heart deliver a train of low-voltage shocks at a rapid rate. During the low-energy shocks, small intrinsic conductivity discontinuities behave as internal “virtual” electrodes. The virtual electrodes serve as activation sites if the field strength depolarizes the tissue beyond the excitation threshold. At low field strengths, only a single virtual pacing site may be created, whereas at slightly higher field strengths, many more activation sites arise, and the time required to excite a given myocardial region decreases. The greater the number of virtual electrodes that are formed as a consequence of external excitation, the easier it is to regularize the temporal aspect of cardiac tissue contractility.
Virtual electrode formation as a therapy is ironically analogous to one of the primary causes of cardiac arrhythmia. Many arrhythmias are caused or maintained by what are clinically called reentry mechanisms. Reentry is a condition in which cardiac tissue continually excites itself, creating reentrant, e.g. circular or tornado-like patterns of excitation. Reentry circuits are described morphologically, for example a macro-reentrant circuit is characterized by rotation around a functional or anatomic line of block. Major anatomical structures are usually involved in defining one or several simultaneous reentry circuits, including the region between superior and inferior venae cavae in the right atrium, and the pulmonary vein region in the left atrium. If the cycle length (CL) of the reentry remains relatively long, one-to-one conduction can remain throughout the entire atrium or ventricle. However, if the CLs of reentry circuits are sufficiently short, waves of excitation produced by the reentrant circuit break up in the surrounding tissue and fibrillation can ensue.
There are distinctions between a regular high frequency rhythm state (tachycardia) and fibrillation. The high frequency state is defined as the presence of a single, constant, and stable reentrant circuit. The fibrillation state is characterized by random activation in which multiple reentrant wavelets of the primary activation wave continuously circulate in directions determined by local excitability, refractoriness, and anatomical structure. The consequence is a multiplicity of spatially localized frequencies created by wave front annihilations. Fibrillation can sometimes be converted to tachycardia, and vice versa, spontaneously or as a result of an intervention, such as drug administration, DC cardioversion/defibrillation, or pacing.
The discussion above is merely provided for general background information and is not intended to be used as an aid in determining the scope of the claimed subject matter.